Evaluation of a Food Supplement with Collagen Hydrolysate and Micronutrients on Skin Appearance and Beauty Effects: A Randomized, Double-Blind ...
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Journal of Clinical and Cosmetic Dermatology
Sci Forschen
Open HUB for Scientific Researc h ISSN 2576-2826 | Open Access
RESEARCH ARTICLE Volume 4 - Issue 4
Evaluation of a Food Supplement with Collagen Hydrolysate and Micronutrients
on Skin Appearance and Beauty Effects: A Randomized, Double-Blind, Placebo-
Controlled Clinical Study with Healthy Subjects
Yvonne Mödinger1,*, Christiane Schön1, Katrin Vogel2, Marianne Brandt2, Stephan Bielfeldt2, and Klaus-Peter Wilhelm2
BioTeSys GmbH, Esslingen, Germany
1
proDERM Institut für Angewandte Dermatologische Forschung GmbH, Schenefeld-Hamburg, Germany
2
*Corresponding author: Mödinger Y, BioTeSys GmbH, Esslingen, Germany; E-mail: y.moedinger@biotesys.de
Received: 19 Dec, 2020 | Accepted: 28 Dec, 2020 | Published: 05 Jan, 2021
Citation: Mödinger Y, Schön C, Vogel K, Brandt M, Bielfeldt S, et al. (2021) Evaluation of a Food Supplement with Collagen Hydrolysate and
Micronutrients on Skin Appearance and Beauty Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Study with Healthy Subjects. J
Clin Cosmet Dermatol 4(4): dx.doi.org/10.16966/2576-2826.158
Copyright: © 2020 Mödinger Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Skin health, skin appearance and skin beauty are influenced by collagen composition of the dermis. Natural aging affects the structural
integrity of the collagen network, resulting in drier skin, wrinkle formation and reduced skin elasticity. Orally ingested hydrolyzed collagen reaches
the skin tissue and exerts beneficial effects on human skin from within. However, not only collagen peptides, but also micronutrients can beneficially
affect skin appearance. Thus, dietary supplements for cosmetic and beauty effects containing combinations of collagen peptides and selected
micronutrients are in demand. Aim of this study was to investigate the effect of a food supplement with collagen hydrolysate and micronutrients on
skin beauty. The test product was assessed for its capability to reduce wrinkles and to improve skin hydration and collagen structure.
Methods: Healthy women (n=72) aged 40-65 years with a light to moderate wrinkle depth were enrolled. Over the 12-week intake period, the test
product Doppelherz system KOLLAGEN BEAUTY (2.5 g collagen peptides and selected micronutrients) or placebo were daily ingested. At baseline,
after 4 and 12 weeks, skin roughness, skin hydration and changes in collagen structure were measured.
Results: Intake of collagen peptides resulted in a reduction of wrinkle depth in the facial area. These effects were evident already after 4 weeks
and the impact was especially pronounced in elderly women. Moreover, intake of collagen peptides slightly improved skin hydration in mid-aged
females.
Conclusion: Results demonstrate a significant mild positive beauty effect after a 12-week application of the collagen supplement and promotes its
concept to support skin beauty from within. The supplement was well tolerated.
Keywords: Collagen; Micronutrients; Skin beauty; Wrinkles; Skin roughness; Skin hydration
Introduction Hydrolyzed collagen is generated from native collagen and is
composed of collagen peptides with low molecular weight. These
Collagen is a moisture-retaining fiber protein that plays an essential
collagen peptides are easily digestible and are well absorbed and
role in the structure of the skin. About 70-80% of connective tissue
distributed in the human body [5]. Importantly, the collagen peptides
consists of collagen, providing firmness and elasticity for the dermis,
reach the skin tissue and are able to remain there for several days [6].
the middle layer of the skin [1]. Thus, the amount, structure and
Indeed, a number of clinical studies confirmed beneficial effects of
composition of collagen in the skin influence its external appearance.
hydrolyzed collagen on human skin [5], for instance by increasing
The moisture content of the skin, the texture of its surface and skin
skin elasticity and hydration [7-12].
elasticity all contributes to skin beauty and are influenced by collagen
characteristics. Skin ageing and the reduction of collagen content may be further
exacerbated by stress- or diet-related deficiencies in micronutrients,
Natural aging affects the structural integrity of the dermis, and
as micronutrients are known to beneficially affect skin appearance
our skin tends to become drier and loses tension and elasticity,
[13-17].
which results in thinner appearance and wrinkle formation. The
main underlying reason is the diminishing collagen content, both The objective of this randomized, placebo-controlled double-
due to reduced endogenous collagen production, and due to collagen blind clinical study was to investigate the cosmetic effect of a food
breakdown, accelerated by external factors, such as UV radiation and supplement with collagen peptides and micronutrients on the quality
certain lifestyle factors (i.e. smoking) [2-4]. of the skin in healthy women, after an intake period of 12 weeks in
J Clin Cosmet Dermatol | JCCD 1
Sci Forschen
Open HUB for Scientific Researc h
Journal of Clinical and Cosmetic Dermatology
Open Access Journal
comparison to placebo. In detail, we assessed the capability of the The DermaTOP blue 3D scanner (EoTech SA, Marcoussis, France)
collagen supplement to reduce wrinkles and skin roughness and to was used to capture the 3D surface structure of the facial crow’s feet area
improve skin hydration and collagen structure. by means of fringe projection at each study visit. From the obtained
3D structure, the roughness parameters Rz (rough skin structure)
Materials and Methods and Ra (fine skin structure) were calculated. Measurement of stratum
Study subjects corneum hydration on the cheek bone area was performed at each
study visit by the electrical capacitance method using a Corneometer®
Healthy female subjects (n=72) at the age of 40-65 years, with a
CM 825 (Courage & Khazaka, Cologne, Germany). Five measurements
BMI of 19-30 kg/m2 and a wrinkle-score of 3-6 were enrolled in the
per measurement area were performed and the mean value was used
study after having given written informed consent (Figure 1). The
for analysis. The confocal microscope VivaScope® 1500 (Lucid Inc.,
suitability of each subject was evaluated according to the inclusion
Rochester, USA) was used for in vivo mapping of the skin to capture
and exclusion criteria. Subjects were excluded in case of pregnancy,
different skin microstructures based on particular refraction indexes.
drug abuse, infectious diseases, insulin-dependent diabetes, cancers or
The optical section resolution was 5 μm and 3 stacks (40 repetitions)
rheumatic disease. Further, subjects with active or past skin disease,
were imaged, starting within the stratum corneum and going down
moles, tattoos or scars at the measurement area were not included in
into the upper dermis (200 μm below the skin surface). The collagen
the study, and participants were advised to refrain from oral or topical
structure in the upper dermis was assessed for its appearance by an
anti-aging products and from the intensive use of skin care products
expert graderat day 1 and day 85 in a blinded manner based on a visual
at the measurement area within one month, as well as to abstain from
analogue scale.
immune-suppressive drugs and antihistamines within 7 days prior to
study start. During the entire study duration, subjects were asked to Methods for safety
maintain their usual dietary habits.
During the study intervention, any adverse events and any used
Confounding effects were controlled, since detailed specifications concomitant medication were documented.
were defined and followed by the subjects. These included, for instance,
to refrain from smoking or water contact in the measurement area Data analysis and statistics
within 2 hours prior to the tests, not to apply any leave on cosmetics Comparison of treatments was performed on differences to baseline
on the measurement area since the evening before, to avoid intensive for each post-application assessment time separately, using a t-Test for
exposure of the measurement area to UV light and not to change independent samples. Further, pair wise comparisons of assessment
regularly used skin care or cleaning products throughout the whole times by treatments were done with paired t-Tests on raw data. No
study period. adjustments for multiplicity were done as data were interpreted in the
The study was approved by the local ethical committee context of an explorative analysis. A significance level of α=0.05 was
(Ethikkommission Schleswig-Holstein, approval code: 122/18 II). The chosen for the supportive data analysis.
study was conducted taking the guidelines for Good Clinical Practice For grading of the collagen structure, images were rated in a blind
(GCP) set forth by the International Council for Harmonisation of manner. Direct comparison of the two time points (day 1 and day 85)
Technical Requirements for Pharmaceuticals for Human Use (ICH) were displayed in pairs and the quality of the collagen structure was
as a guide of reference, and in accordance with the Declaration of rated from -50 (day 1 has the better collagen structure) to +50 (better
Helsinki regarding the treatment of human subjects in a study. collagen structure on day 85 after treatment). For each treatment a
Intervention/ study products statistical comparison to benchmark = ‘0’ (no difference between
day 1 and day 85) was done on raw data by one sample t-Test with a
The liquid study products (25 mL, Queisser Pharma, Flensburg, significance level of α=0.05 for both treatments. The computation of
Germany) were randomly assigned to the study participants in a 2:1 the statistical data was carried out using SAS statistics software (SAS
allocation scheme (verum:placebo). The study products were based on Institute, Cary, USA).
water and pear juice and contained either bovine collagen peptides,
micronutrients (Doppelherz system KOLLAGEN BEAUTY; n=48), or
no bioactive ingredients (placebo; n=24), and were orally ingested on
a daily basis. Doppelherz system KOLLAGEN BEAUTY contained 2.5
g collagen peptides, 100 mg açai berry extract, 80 mg vitamin C, 5 mg
zinc, 3 mg vitamin E, 0.96 mg beta-carotin, 150 μg D-biotin and 150 μg
copper. Both products were of identical appearance and odor.
Study design and measurements
During the 12- week randomized, double-blind, placebo-controlled
clinical study, parameters were assessed at baseline, after 4 and 12 weeks
of intervention. The test areas on face (cheek bone, crow’s feet region)
and thigh (back region) were randomly and balanced assigned to the
left and right side. Before any measurement, and after a resting period
of about 5-10 min, standardized macro photographs of the face were
done by USR-CliP (Unit for Standardized and Reproducible Clinical
Photography) with a high-resolution Hasselblad camera H5D-50c at
day 1 and day 85. Afterwards, subjects were acclimatized for at least 30
Figure 1: CONSORT (Consolidated Standards of Reporting Trials) flow
min in the air-conditioned measurement room at a temperature of 21
diagram of the clinical study.
± 1°C and a relative humidity of 50 ± 5 %.
Citation: Mödinger Y, Schön C, Vogel K, Brandt M, Bielfeldt S, et al. (2021) Evaluation of a Food Supplement with Collagen Hydrolysate
2
and Micronutrients on Skin Appearance and Beauty Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Study with Healthy
Subjects. J Clin Cosmet Dermatol 4(4): dx.doi.org/10.16966/2576-2826.158
Sci Forschen
Open HUB for Scientific Researc h
Journal of Clinical and Cosmetic Dermatology
Open Access Journal
Results and Discussion
Subject characteristics
Seventy-two subjects, aged 54.6 ± 6.1 years, with a mean BMI of
24.45 ± 2.95 kg/m² and a baseline wrinkle score of 4.1 ± 1.0 (light to
moderate wrinkle depth) were included in the study.
Twenty-five subjects (34.7 %) used concomitant therapies, but
none of these were in conflict with study conduct or with the study
objectives. Subjects presented with a baseline capacitance value of 61.7
± 11.7, which corresponds to a normal to dry skin. Baseline average
skin wrinkle depth Ra (23.9 ± 6) and Rz (95.8 ± 24.5) demonstrated a
light to moderate skin wrinkle depth of the study population (Table 1). Figure 2: Change of periorbital wrinkles: roughness parameters Ra (fine
structure) and Rz (rough structure), shown as percent change to baseline
Collagen-mediated decrease in wrinkle depth after intake of the test supplement (blue) and placebo (grey). Study
population: all subjects.
Skin wrinkles in the crow’s feet area were determined by measuring
the fine (Ra) and rough (Rz) skin structure, whereby a decrease in the
skin roughness parameters implies a reduction of skin wrinkles.
Results showed a significantly improved skin surface profile after
intake of the collagen supplement already after 4 weeks. Compared
to baseline, Ra decreased by 4.7 % (day 29) and 2.9 % (day 85) in the
collagen supplement group, while Ra increased by 5.1 % (day 29) and
7.7 % (day 85) in the placebo group (difference Ra day 29: p=0.033; day
85: p=0.011). Taking the collagen supplement improved Rz values by
-5.2% (day 29) and -4.4% (day 85), while Rz increased by 5.1% (day 29)
and 6.0% (day 85) in the placebo group (difference Rz day 29: p=0.043;
day 85: p=0.021) (Figure 2).
Effects on wrinkle depth were particularly pronounced in older
subjects aged 51-65 years (n=59) (day 85: Ra: collagen supplement Figure 3: Change of periorbital wrinkles: roughness parameters Ra (fine
-4.6 % vs. placebo: +9.9 %; p=0.006; Rz: collagen supplement -6.5 % structure) and Rz (rough structure) shown as percent change to baseline
vs. placebo +7.6 %; p=0.012). Effects were even more pronounced in after intake of the test supplement (blue) and placebo (grey). Study
women aged 56-65 years (n=30) after 12 weeks of application. Here population: women aged 56-65 years (n=30).
roughness parameters improved (Ra: -8.8 %; Rz: -10.8 %) under
supplementation with collagen peptides, while parameters worsened
(Ra: +14.2 %; Rz: + 12.2 %) in the placebo group (difference Ra and Rz
p
Sci Forschen
Open HUB for Scientific Researc h
Journal of Clinical and Cosmetic Dermatology
Open Access Journal
measuring technique was not sensitive enough to detect subtle
changes, for instance regarding the different collagen types. Confocal
microscopy records variations in the refractive index of different
microstructures, and these refractive indices are similar between
all collagen types. Moreover, albeit confocal microscopy is able to
detect differences in the degree of collagen diffuseness, changes
towards more diffuse collagen structures, present in younger and
more subtle skin, might not get evident over a time period of 3
months. In contrast, in the study by Asserin J, et al. including 106
healthy women, a reduced collagen fragmentation after the intake of
10 g fish peptides (4 times the dose of the study product) could be
observed by using confocal microscopy [22]. These results support,
that intake of external collagen peptides impacts the degree of
fragmentation in the human dermis.
Product safety
Overall, both study products were well tolerated. In total, twelve
adverse events were documented by 9 subjects during study conduct
Figure 5: Skin capacitance as parameter for skin hydration, shown as in the collagen group, where of one was classified as being serious
percent change to baseline after intake of the test supplement (blue) and
(lumbago with short inpatient hospitalization), but none was related
placebo (grey). Study population: women aged 45-55 years.
to the test product. Equal amounts of adverse events (eleven), albeit
in study population half as large, were reported by 7 subjects in the
placebo group. None of these adverse events was classified as serious,
Collagen-mediated improvement of skin hydration in mid- but for two adverse events a relation to the placebo product could
aged females not be excluded (Exacerbation of neurodermatitis with eczema on
In this study skin hydration was measured with the electrical hand and on skin under left eye). Overall, the study confirmed the
capacitance method using the Corneometer. No significant differences good safety profile for the collagen supplement. In both study groups,
over the 12-week intervention period were observed between the study subjects confirmed the easy and uncomplicated intake of study
groups, when referring to the whole study population. However, when products (100% of agreement), which were well tolerated.
focusing on mid-aged females (45-55 years, n=36), skin hydration
Conclusion
improved in the collagen supplement group (+4.3 %; day 29; +1.5 %;
day 85), with the skin being slightly moister compared to the placebo Concluding, in this study we documented a significant mild
group after 12 weeks (p=0.091) (Figure 5). positive cosmetic effect on an important anti-aging parameter, which
is reduction of wrinkle depth in the facial area after a 12-week lasting
Similar to the herein presented results, skin moisture was positively application of the collagen test product compared to placebo. Of note,
influenced in women aged 35-55 years by a 8-week treatment with this positive effect was already evident after 4 weeks. The appearance
collagen hydrolysate (2.5 g or 5 g) and results did also not reach of the skin was positively altered by a significant improvement in fine
statistical significance [21]. Likewise, in the study by Schwartz and and coarse structures. The data show that especially older women
Park, water content was higher (+ 8 %) after 12 week-intake of 0.3 g with already more pronounced wrinkle relief may benefit from the
collagen peptides, hyaluronic acid and chondroitin sulfate, however application of the collagen supplement.
the increase was not significant [19].
Overall, the study results are in line with other clinical studies
Another clinical trial, including women with normal to dry
investigating effects of collagen hydrolysate or of combination
skin, showed that the 8-week-intake of 10 g fish or porcine collagen
products with collagen hydrolysates as main ingredient [5,10].
resulted in a significant increase in skin hydration (+ 12 % or + 28 %,
However, the extent and characteristic of the impact differs between
respectively) [22]. Of note, the dose of collagen peptides used in the
investigations. External factors might impact study results and hamper
study by Asserin J, et al. [22] was higher compared to the one present
direct comparisons. Factors contributing to these differences are, for
in the collagen study product. A further study describes a significant
instance, differing study collectives and designs, seasonal factors,
increase in skin hydration in males and females after daily intake of 3 g
differences in applied methodologies and dosages of nutrients, as well
collagen peptides, however after a longer supplementation period (12
as normal physiological variations.
weeks), compared to the herein performed study [23].
Aside from collagen peptides, the test product contains different
The influence of the collagen supplement on skin hydration in
micronutrients, including vitamin C, zinc, vitamin E, β-carotin, biotin
this study might have been confounded by seasonal changes. The
study started in January and was finished in April, and dryness in the and copper. These micronutrients can contribute to the maintenance
ambient air might have changed within this time period. of normal skin and connective tissue, as these vitamins and minerals
function as cofactors in various metabolic processes related to skin
Collagen microstructure was not affected by intake of the physiology and collagen metabolism [13-15]. Thus, the herein tested
collagen supplement collagen supplement benefits from the interplay of the contained
collagen peptides with selected essential nutrients.
Collagen microstructure, as assessed by confocal microscopy,
appeared indifferent between placebo and the collagen product in In summary, the obtained results support the product concept of
this study. No significant differences were found between treatments Doppelherz system KOLLAGEN BEAUTY to support skin beauty
or assessment times (data not shown). Presumably, the selected from within.
Citation: Mödinger Y, Schön C, Vogel K, Brandt M, Bielfeldt S, et al. (2021) Evaluation of a Food Supplement with Collagen Hydrolysate
4
and Micronutrients on Skin Appearance and Beauty Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Study with Healthy
Subjects. J Clin Cosmet Dermatol 4(4): dx.doi.org/10.16966/2576-2826.158Sci Forschen
Open HUB for Scientific Researc h
Journal of Clinical and Cosmetic Dermatology
Open Access Journal
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Citation: Mödinger Y, Schön C, Vogel K, Brandt M, Bielfeldt S, et al. (2021) Evaluation of a Food Supplement with Collagen Hydrolysate
5
and Micronutrients on Skin Appearance and Beauty Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Study with Healthy
Subjects. J Clin Cosmet Dermatol 4(4): dx.doi.org/10.16966/2576-2826.158You can also read
